Axl (also known as: UFO, ARK, Tyro7) is a receptor tyrosine kinase belonging to a TAM family (Axl, Mer and Tyro3) cloned from tumor cells. Gas6 (growth-arrest-specific protein 6) gene specifically expressed at the time of cell proliferation arrest has been cloned. The expressed protein is known as a ligand for Axl. Axl activated by binding of Gas6 transfers a signal via phosphorylation. Since the signal activates an Erk1/2 pathway or a PI3K/Akt pathway, the activation of Axl is known to be involved in pathologic conditions of cancers, immune system diseases, circulatory system diseases, and the like (see, Non-Patent Literature 1).
In particular, the relation between Axl and various types of cancers is well known. For example, it is known that the expression of Axl is involved in metastasis and prognosis of breast cancer (see, Non-Patent Literature 2), and that Axl is involved in the pathologic conditions of acute myeloid leukemia (AML) (see Non-Patent Literature 3). Therefore, it is considered that compounds which inhibit the activation of Axl are useful for treatment of various types of cancers, immune system diseases, and circulatory system diseases.
By the way, as prior art of the compound of the present invention, a compound represented by the general formula (A):
(wherein AA represents a 6-membered aromatic ring or a 5- to 6-membered heteroaromatic ring, which may have a substituent such as halogen; LA represents —O—, —S—, —N(C(O)RA)—, or the like; RA represents hydrogen, an acyl group, or the like; R1A represents hydrogen, a C1-C6 alkyl group, or the like; R2A represents hydrogen, a substituted or unsubstituted aliphatic compound, or the like; R3A represents a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aromatic ring, or the like; and jA represents an integer from 0 to 6 (where the definitions of the groups are excerpted)) is known to be a VEGF kinase inhibitor (see Patent Literatures 1, 2, and 3).
Furthermore, a compound represented by the general formula (B):
(wherein XB represents ═N— or ═C(-L6B-R6B)—; L1B, L2B, L3B, L4B, and L6B independently represent a bond, —C(O)—N(R7B)—, a substituted or unsubstituted alkylene group, or the like; R1B, R2B, R3B, R6B, and R7B independently represent hydrogen, halogen, —NH2, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, or the like; aB represents an integer from 0 to 2; and bB represents an integer from 0 to 5 (where the definitions of the groups are excerpted)) is known to be a Lrrk-2 inhibitor (see Patent Literature 4).
A compound having pyrrolo pyrimidine derivative having a pyridone ring, represented by the following structural formula:
is a compound of the present invention. Any of the prior art literatures neither mention nor suggest that the compound of the present invention has significant Axl inhibitory activity.